Vision and Mission

The human brain is energetically expensive, yet the key factors governing its heterogeneous energy distributions across cortical regions to support its diversity of functions remain unexplored. We envision building a 3D digital cortical energy atlas feeding the energetic costs of all cellular and synaptic activities into a high-resolution stereological atlas of the human cortex based on neuropil distributions.

As proof of concept, the cellular and synaptic densities were derived respectively from ex vivo histological staining data from BigBrain Project and in vivo PET imaging using synaptic vesicle glycoprotein 2A (SV2A) radioligand [11C]UCB-J. The atlas was validated with PET-measured oxidative glucose metabolism at the voxel level using combined measurements of glucose and oxygen metabolism for awake but eyes closed state. In the first test of this concept for a brain energy atlasof the human brain, a 3D cortical activity map was calculated to predict the heterogeneous activity rates across all cortical regions, which revealed that resting brain is indeed active with neuronal activity rates averaging around 1.2 Hz, comprising around 70% of the glucose oxidation of the cortex.

This framework reveals design principles in energy-constrained human cortical circuits across multiple spatial scales, where our future goals are to measure the neuropil density on a subject-by-subject basis for individualized energy budgets which could be compared with in vivo measurements of brain energy dynamics (e.g., by calibrated fMRI).